Influence of energy deficiency on the subcellular processes of Substantia Nigra Pars Compacta cell for understanding Parkinsonian neurodegeneration

Abstract Parkinson’s disease (PD) is the second most prominent neurodegenerative disease around the world. Although it is known that PD is caused by the loss of dopaminergic cells in substantia nigra pars compacta (SNc), the decisive cause of this inexorable cell loss is not clearly elucidated. We h...

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Autores principales:	Vignayanandam Ravindernath Muddapu, V. Srinivasa Chakravarthy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/015cf1e0f14e490994ec591202e8e513
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spelling	oai:doaj.org-article:015cf1e0f14e490994ec591202e8e5132021-12-02T13:51:06ZInfluence of energy deficiency on the subcellular processes of Substantia Nigra Pars Compacta cell for understanding Parkinsonian neurodegeneration10.1038/s41598-021-81185-92045-2322https://doaj.org/article/015cf1e0f14e490994ec591202e8e5132021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81185-9https://doaj.org/toc/2045-2322Abstract Parkinson’s disease (PD) is the second most prominent neurodegenerative disease around the world. Although it is known that PD is caused by the loss of dopaminergic cells in substantia nigra pars compacta (SNc), the decisive cause of this inexorable cell loss is not clearly elucidated. We hypothesize that “Energy deficiency at a sub-cellular/cellular/systems level can be a common underlying cause for SNc cell loss in PD.” Here, we propose a comprehensive computational model of SNc cell, which helps us to understand the pathophysiology of neurodegeneration at the subcellular level in PD. The aim of the study is to see how deficits in the supply of energy substrates (glucose and oxygen) lead to a deficit in adenosine triphosphate (ATP). The study also aims to show that deficits in ATP are the common factor underlying the molecular-level pathological changes, including alpha-synuclein aggregation, reactive oxygen species formation, calcium elevation, and dopamine dysfunction. The model suggests that hypoglycemia plays a more crucial role in leading to ATP deficits than hypoxia. We believe that the proposed model provides an integrated modeling framework to understand the neurodegenerative processes underlying PD.Vignayanandam Ravindernath MuddapuV. Srinivasa ChakravarthyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-36 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vignayanandam Ravindernath Muddapu V. Srinivasa Chakravarthy Influence of energy deficiency on the subcellular processes of Substantia Nigra Pars Compacta cell for understanding Parkinsonian neurodegeneration
description	Abstract Parkinson’s disease (PD) is the second most prominent neurodegenerative disease around the world. Although it is known that PD is caused by the loss of dopaminergic cells in substantia nigra pars compacta (SNc), the decisive cause of this inexorable cell loss is not clearly elucidated. We hypothesize that “Energy deficiency at a sub-cellular/cellular/systems level can be a common underlying cause for SNc cell loss in PD.” Here, we propose a comprehensive computational model of SNc cell, which helps us to understand the pathophysiology of neurodegeneration at the subcellular level in PD. The aim of the study is to see how deficits in the supply of energy substrates (glucose and oxygen) lead to a deficit in adenosine triphosphate (ATP). The study also aims to show that deficits in ATP are the common factor underlying the molecular-level pathological changes, including alpha-synuclein aggregation, reactive oxygen species formation, calcium elevation, and dopamine dysfunction. The model suggests that hypoglycemia plays a more crucial role in leading to ATP deficits than hypoxia. We believe that the proposed model provides an integrated modeling framework to understand the neurodegenerative processes underlying PD.
format	article
author	Vignayanandam Ravindernath Muddapu V. Srinivasa Chakravarthy
author_facet	Vignayanandam Ravindernath Muddapu V. Srinivasa Chakravarthy
author_sort	Vignayanandam Ravindernath Muddapu
title	Influence of energy deficiency on the subcellular processes of Substantia Nigra Pars Compacta cell for understanding Parkinsonian neurodegeneration
title_short	Influence of energy deficiency on the subcellular processes of Substantia Nigra Pars Compacta cell for understanding Parkinsonian neurodegeneration
title_full	Influence of energy deficiency on the subcellular processes of Substantia Nigra Pars Compacta cell for understanding Parkinsonian neurodegeneration
title_fullStr	Influence of energy deficiency on the subcellular processes of Substantia Nigra Pars Compacta cell for understanding Parkinsonian neurodegeneration
title_full_unstemmed	Influence of energy deficiency on the subcellular processes of Substantia Nigra Pars Compacta cell for understanding Parkinsonian neurodegeneration
title_sort	influence of energy deficiency on the subcellular processes of substantia nigra pars compacta cell for understanding parkinsonian neurodegeneration
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/015cf1e0f14e490994ec591202e8e513
work_keys_str_mv	AT vignayanandamravindernathmuddapu influenceofenergydeficiencyonthesubcellularprocessesofsubstantianigraparscompactacellforunderstandingparkinsonianneurodegeneration AT vsrinivasachakravarthy influenceofenergydeficiencyonthesubcellularprocessesofsubstantianigraparscompactacellforunderstandingparkinsonianneurodegeneration
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Influence of energy deficiency on the subcellular processes of Substantia Nigra Pars Compacta cell for understanding Parkinsonian neurodegeneration

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